technetium-tc-99m-tetrofosmin and Arteriosclerosis-Obliterans

We investigated efficacy and safety of implantation of autologous bone marrow mononuclear cells plus platelets, including endothelial progenitor cells (EPCs), for recovering refractory chronic peripheral arterial disease (PAD) using visual and quantitative analyses by 99mTc-tetrofosmin (TF) perfusion scintigraphy, and also investigated various quantitative assessments objectively. We performed 12 consecutive cases and 19 limbs and hands with severe chronic PAD that were almost Fontaine class IV (11/12 cases, about 92%) in this trial. This treatment was very effective in relieving severe pain of PAD, especially for Buerger's disease. We used a visual analog scale (VAS) for measurement of pain level. The maximum pain level before implantation was 66.5+/-5.0 mm, and it decreased to 12.1+/-2.2 mm after implantation (p < 0.001). Rest pain in legs and fingers was resolved in 11 cases (11/12 cases, 92%). All patients could measure pain-free walking time on a treadmill, which improved remarkably (140+/-53 s before implantation vs. 451+/-74 s after implantation, p = 0.034). Resting ankle brachial pressure index (ABI) in legs implanted with bone marrow mononuclear cells was also improved (0.65+/-0.08 before implantation vs. 0.73+/-0.07 after implantation, p = 0.055). According to 99mTc-TF perfusion scintigraphy, the proximal area (region from knee to ankle) was 1.32+/-0.10 before implantation versus 1.56+/-0.11 after implantation (p = 0.007). 99Tc-TF perfusion scintigraphy in the distal area (region from ankle to end of toes, or from wrist to end of fingers) was 0.79+/-0.06 before implantation versus 0.83+/-0.06 after implantation (p = 0.29). Ischemic legs and hands that were injected showed increased perfusion blood flow. 99mTc-TF perfusion scintigraphy was effective to estimate visual and quantitative analysis of collateral vessels in neovascularization. We were successful with this new treatment for the most severe, chronic PAD that was not curable by any of the current treatments. Thus, this therapeutic angiogenesis could be a new strategy for saving severe ischemic limbs and hands.

Topics: Aged; Arteriosclerosis Obliterans; Bone Marrow Cells; Bone Marrow Transplantation; Chronic Disease; Diabetic Angiopathies; Female; Gangrene; Humans; Male; Middle Aged; Neovascularization, Physiologic; Organophosphorus Compounds; Organotechnetium Compounds; Peripheral Vascular Diseases; Radionuclide Imaging; Radiopharmaceuticals; Thromboangiitis Obliterans

One problem of vascular angiogenesis therapy is the lack of reliable methods for evaluating blood flow in the microcirculation. We aimed to assess whether (99m)Tc-macroaggregated albumin perfusion scintigraphy ((99m)Tc-MAA) predicts quantitated blood flow after therapeutic angiogenesis in patients with peripheral artery disease.. Forty-six patients with peripheral artery disease were treated with bone marrow mononuclear cell implantation (BMCI). Before and 4 wk after BMCI, blood flow was evaluated via transcutaneous oxygen tension (TcPO2), ankle-brachial index, intravenous (99m)Tc-tetrofosmin perfusion scintigraphy ((99m)Tc-TF), and intraaortic (99m)Tc-MAA.. Four weeks after BMCI, TcPO2 improved significantly (20.4 ± 14.4 to 36.0 ± 20.0 mm Hg, P < 0.01), but ankle-brachial index did not (0.65 ± 0.30 to 0.76 ± 0.24, P = 0.07). Improvement in (99m)Tc-TF count (0.60 ± 0.23 to 0.77 ± 0.29 count ratio/pixel, P < 0.01) and (99m)Tc-MAA count (5.21 ± 3.56 to 10.33 ± 7.18 count ratio/pixel, P = 0.02) was observed in the foot region but not the lower limb region, using both methods. When these data were normalized by subtracting the pixel count of the untreated side, the improvements in (99m)Tc-TF count (-0.04 ± 0.26 to 0.08 ± 0.32 count ratio/pixel, P = 0.04) and (99m)Tc-MAA count (1.49 ± 3.64 to 5.59 ± 4.84 count ratio/pixel, P = 0.03) in the foot remained significant. (99m)Tc-MAA indicated that the newly developed arteries were approximately 25 μm in diameter.. BMCI induced angiogenesis in the foot, which was detected using (99m)Tc-TF and (99m)Tc-MAA. (99m)Tc-MAA is a useful method to quantitate blood flow, estimate vascular size, and evaluate flow distribution after therapeutic angiogenesis.

Topics: Aged; Ankle Brachial Index; Arteries; Arteriosclerosis Obliterans; Bone Marrow Transplantation; Female; Foot; Humans; Lower Extremity; Male; Middle Aged; Neovascularization, Physiologic; Organophosphorus Compounds; Organotechnetium Compounds; Oxygen; Pain; Pain Measurement; Peripheral Arterial Disease; Positron-Emission Tomography; Radiopharmaceuticals; Regional Blood Flow; Technetium Tc 99m Aggregated Albumin; Thromboangiitis Obliterans; Treatment Outcome

The authors have hereby proposed a method to diagnose lower-limb muscular ischaemia by means of scintigraphy, used in 35 patients suffering from atherosclerosis obliterans with stage IIB and III A chronic arterial insufficiency of limbs. To do so, administration of the radioactive agent "Myoview" (⁹⁹m)Tc-tetrophosmine) manufactured by the "Nycomed" Company into a patient's peripheral vein was followed by assessing its accumulation in lower-limb muscles at rest and after standard physical load. Alterations in the parameters studied relative to the norm made it possible to judge on the presence of lower-limb circulatory impairments. The method proved highly efficient, thus making it possible to use it for both therapeutic decision-making and probably in future for dynamic control after the treatment performed. Minimally invasive nature and simplicity in use of the methodology open wide possibilities for its use.

Topics: Adult; Arteriosclerosis Obliterans; Diagnosis, Differential; Humans; Injections, Intra-Arterial; Male; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Perfusion Imaging; Radiopharmaceuticals; Regional Blood Flow; Reproducibility of Results; Severity of Illness Index

Twenty-one patients with arteriosclerosis obliterans (ASO) were studied with 99mTc-tetrofosmin exercise leg perfusion scintigraphy using the delayed administration method. In this method, tracer was injected 4 minutes after termination of symptom-limited repetitive climbing of a stair to validate prolonged vasodilatation in an ischemic lower limb after exercise. Visual and quantitative analyses were performed to evaluate a diseased leg using dynamic and static images. On a posterior whole body image, all cases except one showed decreased foot uptake in the affected side (affected normal ratio; ANR = 0.82 +/- 0.14). On dynamic images, 9 cases showed transient hyper-accumulation (blush phenomenon) only in the thigh of the affected side suggesting that this valuable finding may be a useful diagnostic sign to distinguish a diseased leg. Sensitivity and positive predictive value were 71.4% and 93.8% to detect a diseased leg based on more than one finding of non-visualization of ilio-femoral artery, muscle-soft tissue blush, and early venous return in a dynamic study. Moreover, a low uptake of ANR of below 0.90 in the foot in the static study gave an improved sensitivity of 85.7%. The transit time of the diseased legs (12.0 +/- 3.1 sec.) which was determined as the interval between the time of arterial and venous peak counts was significantly shorter than that of normal legs (17.3 +/- 4.5 sec.; p < 0.0001, paired t-test). The cases with blush phenomenon showed significantly higher thigh ANR (1.04 +/- 0.11) than those without (0.94 +/- 0.08; p < 0.05, unpaired t-test). These results could reflect prolongation of a hypervascular state after exercise in a diseased leg which sometimes induced blush phenomenon at arterial phase and high leg uptake at static phase. This scintigraphy is useful for the detection of a diseased leg as well as for grasping changes of vascular regulation after stress in patients with ASO.

Topics: Aged; Aged, 80 and over; Arteriosclerosis Obliterans; Exercise Test; Female; Humans; Ischemia; Leg; Male; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals